U.S. patent application number 11/369992 was filed with the patent office on 2007-09-13 for method of powder coating medical devices.
This patent application is currently assigned to BOSTON SCIENTIFIC SCIMED, INC.. Invention is credited to Gerald Fredrickson, M. J. Timm.
Application Number | 20070212547 11/369992 |
Document ID | / |
Family ID | 38324097 |
Filed Date | 2007-09-13 |
United States Patent
Application |
20070212547 |
Kind Code |
A1 |
Fredrickson; Gerald ; et
al. |
September 13, 2007 |
Method of powder coating medical devices
Abstract
A method of creating a polymer coating on a medical device by
powder coating the medical device with a powder material comprising
a polymer and applying a solvent onto the powder coating to
coalesce the powder coating into a continuous polymer film. A
therapeutic agent may be mixed into the powder material, mixed into
the coalescing solvent, or incorporated into the resulting polymer
film. Also provided is a medical device having a polymer coating
wherein the polymer coating is created according to the methods of
the present invention.
Inventors: |
Fredrickson; Gerald;
(Westford, MA) ; Timm; M. J.; (Littleton,
MA) |
Correspondence
Address: |
KENYON & KENYON LLP
1500 K STREET N.W.
SUITE 700
WASHINGTON
DC
20005
US
|
Assignee: |
BOSTON SCIENTIFIC SCIMED,
INC.
|
Family ID: |
38324097 |
Appl. No.: |
11/369992 |
Filed: |
March 8, 2006 |
Current U.S.
Class: |
428/411.1 ;
427/180; 427/2.1; 427/337 |
Current CPC
Class: |
A61L 31/10 20130101;
A61L 2300/00 20130101; B05D 3/0254 20130101; Y10T 428/31504
20150401; A61L 31/16 20130101; B05D 2258/00 20130101; B05D 3/105
20130101; B05D 3/0493 20130101; A61L 31/10 20130101; B05D 1/06
20130101; C08L 53/02 20130101 |
Class at
Publication: |
428/411.1 ;
427/002.1; 427/180; 427/337 |
International
Class: |
A61L 33/00 20060101
A61L033/00; B05D 1/12 20060101 B05D001/12; B05D 3/10 20060101
B05D003/10; B32B 27/00 20060101 B32B027/00 |
Claims
1. A method of coating a medical device, comprising the steps of:
(a) applying a powder coating to a medical device, wherein the
powder coating comprises a polymer; (b) applying a solvent to the
powder coating, wherein the solvent coalesces the polymer; and (c)
removing the solvent.
2. The method of claim 1, wherein the medical device is a
stent.
3. The method of claim 1, wherein the step of applying a powder
coating is performed by an electrostatic powder coating
process.
4. The method of claim 1, wherein the step of applying a solvent to
the powder coating comprises spraying the solvent onto the powder
coating.
5. The method of claim 1, further comprising the step of selecting
a solvent that dissolves, solubilizes, or emulsifies the
polymer.
6. The method of claim 1, further comprising the step of selecting
a solvent that allows the polymer to flow at a temperature below
the T.sub.g of the polymer.
7. The method of claim 1, wherein the step of removing the solvent
comprises evaporating the solvent.
8. The method of claim 7, wherein the step of evaporating the
solvent comprises applying low heat to the powder coating.
9. The method of claim 7, wherein the step of evaporating the
solvent comprises vacuum drying the solvent.
10. The method of claim 1, wherein the powder coating further
comprises a therapeutic agent.
11. The method of claim 1, wherein the solvent further comprises a
therapeutic agent.
12. The method of claim 1, further comprising the step of
incorporating a therapeutic agent into the polymer film.
13. A method of coating a medical device, comprising the steps of:
(a) applying a powder coating to a medical device, wherein the
powder coating comprises a polymer; (b) applying a solvent to the
powder coating; and (c) applying low heat to the powder
coating.
14. The method of claim 13, wherein applying low heat to the powder
coating causes the polymer to coalesce.
15. The method of claim 13, wherein the step of applying a powder
coating is performed by an electrostatic powder coating
process.
16. The method of claim 13, wherein the step of applying a solvent
to the powder coating comprises spraying the solvent onto the
powder coating.
17. The method of claim 13, further comprising the step of
selecting a solvent that dissolves, solubilizes, or emulsifies the
polymer.
18. The method of claim 13, further comprising the step of
selecting a solvent that allows the polymer to flow at a
temperature below the T.sub.g of the polymer.
19. The method of claim 13, further comprising the step of removing
the solvent.
20. The method of claim 19, wherein the step of removing the
solvent comprises evaporating the solvent.
21. The method of claim 20, wherein the step of evaporating the
solvent comprises applying low heat to the powder coating.
22. The method of claim 20, wherein the step of evaporating the
solvent comprises vacuum drying the solvent.
23. The method of claim 13, wherein the powder coating further
comprises a therapeutic agent.
24. The method of claim 13, wherein the solvent further comprises a
therapeutic agent.
25. The method of claim 13, further comprising the step of
incorporating a therapeutic agent into the polymer film.
26. A medical device having a polymer coating, wherein the polymer
coating is formed by the method of claim 1.
27. A medical device having a polymer coating, wherein the polymer
coating is formed by the method of claim 13.
Description
TECHNICAL FIELD
[0001] The present invention relates to methods of coating medical
devices with a polymer coating.
BACKGROUND
[0002] Many implantable medical devices are coated with a
therapeutic agent or drug that acts to improve the effectiveness of
the device. One such example of a drug-coated implantable medical
device is a coronary stent. Coronary stents are tubular structures
formed in a mesh-like pattern that are designed to be inserted into
a coronary artery across an area of blockage that has been opened
by an angioplasty procedure. The stent serves as a permanent
scaffolding for the newly widened coronary artery.
[0003] In many instances, however, the stented artery becomes
narrowed again in a process known as restenosis, which results from
vessel wall injury, local inflammation, and tissue remodeling
following the balloon angioplasty and stenting. Therefore, many
coronary artery stents are coated with a drug, such as paclitaxel
or other therapeutic agent, that acts to inhibit the processes that
cause restenosis.
[0004] Stents can be coated by various conventional coating
processes, such as spray coating, electrostatic spraying, or dip
coating. These prior processes have various advantages and
disadvantages. For example, spray coating methods often have low
transfer efficiencies because much of the coating solution is lost
in excessive overspraying. Transfer efficiencies are important as
some coating materials are expensive, such as therapeutic agents,
drugs and polymers. Also, certain spray coating methods, such as
gas-assisted spray coating, can impart a high degree of shear to
the coating solution, resulting in damage to shear sensitive
coating materials.
SUMMARY OF THE INVENTION
[0005] The present invention includes embodiments directed to a
method of powder coating medical devices. In one embodiment, a
medical device is coated with a powder coating wherein the powder
coating comprises a polymer. A solvent is applied to the powder
coating to coalesce the polymer in the powder coating into a
continuous polymer film. The solvent may be sprayed onto the powder
coating. The solvent may be removed by evaporation at room
temperature, or under low heat, or under vacuum drying. A
therapeutic agent may be mixed into the powder coating material,
mixed into the coalescing solvent, or incorporated into the
resulting polymer film.
[0006] In another embodiment, a medical device is coated with a
powder coating wherein the powder coating comprises a polymer; a
solvent is applied to the powder coating; and heat is applied to
the powder coating. The application of low heat to the powder
coating may assist in coalescing the polymer, evaporating the
solvent, or both.
[0007] The present invention also includes embodiments directed to
medical devices coated with polymer films formed by the coating
methods of the present invention.
DETAILED DESCRIPTION
[0008] The present invention includes embodiments directed to a
method of powder coating a medical device. The powder coating
material used in this invention comprises polymers which may be
available in powder form, or a polymer in solution may be converted
into a powder formulation by various methods known in the art,
including spray drying, pelletization, micronization, and cryogenic
cooling with grinding. The powder coating material may be in the
form of a fine powder with particle sizes suitable for use in
conventional powder coating processes. The powder coating material
can be applied onto the medical device by various known methods
including the use of fluid beds, electrostatic fluid beds, and
electrospray guns (including corona-charged and tribo-charged
guns). The thickness of the coating will vary depending upon the
medical device and desired function of the coating.
[0009] Powder coating may be restricted to certain portions of the
medical device by masking techniques that are known in the art. In
conventional masking techniques, certain areas of the medical
device may be physically covered or blocked to prevent powder
deposition. In electrostatic masking techniques, a charged body is
used to redirect or repel the powder coating material. In one
example, such masking techniques may be used to restrict the powder
coating to the outer diameter of a stent.
[0010] The polymers used in the present invention are those having
the desired biological, chemical, physical, mechanical, or
pharmacologic properties for its use in the coating of medical
devices and implantable medical devices in particular. For example,
in drug-eluting stents, the polymers used can be
styrene-isobutylene block copolymers such as
styrene-isobutylene-styrene tri-block copolymers (SIBS) and other
block copolymers such as styrene-ethylene/butylene-styrene (SEBS).
The polymers may have a glass transition temperature (T.sub.g) in
the range of -120.degree. C. to 200.degree. C. in order to
facilitate low temperature curing. Where room temperature curing is
desired, the polymers may have a T.sub.g in the range of 20.degree.
C. to 200.degree. C.
[0011] A solvent is then applied to the powder coating by various
methods known in the art, including spraying, electrostatic
spraying, dip coating, and the like. An electrostatic fine mist
spray of solvent may be used in order to minimize disturbance to
the powder layer. The solvent coalesces the polymer in the powder
coating into a continuous polymer film. The solvent may accomplish
this by dissolving, solubilizing, or emulsifying the polymer, or
otherwise allowing the polymer chains to flow together at a
temperature below its T.sub.g to yield a continuous polymer film.
The coalescence may occur at room temperature or under low heat. In
embodiments where a therapeutic agent is mixed into the powder
coating material or solvent, the heat used to coalesce the polymer
is sufficiently low that the therapeutic agent does not
significantly degrade. For example, in a coronary stent coated with
a powder coating mixture of SIBS and paclitaxel, low heat in the
range of 30.degree. C. to 75.degree. C. for a duration of one to
ten hours would yield a continuous polymer film with little or no
drug degradation.
[0012] Various solvents that are capable of coalescing the polymer
particles into a continuous film are suitable for use in the
solvent coalescing step. Solvents that allow good flow of the
polymer chains at low temperatures may be used, including solvents
that dissolve the polymer. In certain embodiments of the present
invention where a therapeutic agent is mixed into the solvent,
solvents are further selected for their ability to dissolve or not
dissolve the drug, depending upon the desired drug release
characteristics of the resulting polymer film. In the example of a
coronary stent coated with paclitaxel and SIBS, tetrahydrafuran
(THF) may be preferred for its ability to dissolve both the drug
and polymer. In other instances, however, it may be desirable to
select a solvent that does not dissolve the drug. For example,
where a particulate, non-homogenous coating of paclitaxel is
desired, THF blended with a solvent in which paclitaxel is not
soluble, such as toluene or xylene, would be preferred. With the
appropriate selection of solvents and coalescing conditions such as
temperature, one of skill in the art would be able to create
polymer coatings with varying properties, including ones that have
the desired drug release characteristics. Also, one of skill in the
art could use the method of the present invention to closely
replicate the stent coatings that are formed by conventional spray
coating processes.
[0013] Simultaneous with or after the step of coalescing the
polymer, the solvent is removed from the coating by evaporation.
Low heat that can be applied to assist in coalescing the powder
coating may also be used to serve the purpose of assisting in
solvent evaporation. Vacuum drying could also be used to assist in
evaporating the solvent. In the example of a SIBS/paclitaxel-coated
stent, one to ten hours of low heat in the range of 30.degree. C.
to 75.degree. C. under vacuum would be sufficient to fully remove
the solvent. Because there is an inverse relationship between
drying duration and temperature, shorter drying times could be
achieved at higher temperatures, or alternatively, lower
temperatures could be used with longer drying times. With the
appropriate selection of drying conditions, including duration and
application of heat or vacuum, one of skill in the art would be
able to create coatings with varying properties.
[0014] In certain embodiments of the present invention, a
therapeutic agent is dispersed within the resulting polymer
coating. The therapeutic agent may be added at various steps in the
method of the present invention. In one embodiment, the therapeutic
agent may be introduced into the powder coating material. The
therapeutic agent may be available in powder form, or may be
converted into a powder formulation by various known methods such
as spray drying, pelletization, micronization, and cryogenic
cooling with grinding, and then mixed with the polymer powder.
Alternatively, the polymer and drug may be mixed in a solution,
suspension, or dispersion, and the combined mixture may be
converted into a powder formulation.
[0015] In other embodiments, the therapeutic agent may be mixed
into the solvent that is used to coalesce the powder coating. The
solvent may or may not dissolve the drug, depending upon the
desired drug release characteristics of the resulting polymer film.
In still other embodiments, the therapeutic agent may be
incorporated into the polymer film by conventional methods such as
spray coating, dip coating, vacuum impregnation, or electrophoretic
transfer, as a subsequent step after the polymer film is
created.
[0016] The powder coating method of the present invention may also
be applied repetitively, or in combination with conventional spray
coating techniques, which may, in some cases, result in the
creation of multiple discrete layers. For example, a first coating
can be applied to a medical device by conventional techniques,
followed by a second coating applied over the first coating using
the powder coating method of the present invention. Alternatively,
a first coating can be applied by the powder coating method of the
present invention, followed by a second coating applied over the
first coating using conventional techniques. With these techniques,
two or more discrete layers can be created where the outer layers
can be used to control the diffusion rate of therapeutic agent
released from the inner layers.
[0017] Coating medical devices by powder coating methods in
accordance with the present invention offers several advantages
over other types of coating methods. In general, powder coating
methods have a very high transfer efficiency, approaching nearly
100% in some cases. This is because the powder coating material is
dry and any overspray can readily be retrieved and reused. This
advantage is particularly beneficial where expensive polymers
and/or drugs are being applied to medical devices.
[0018] In general, powder coating equipment is also less expensive
and less costly to maintain than other conventional spray coating
equipment. Powder coating further has the advantages of not
applying damaging shear forces to fragile coating materials and
being suitable for use with coating materials that are not easily
soluble in typical spray coating solvents.
[0019] The use of solvents to coalesce the polymer of the powder
coating material also offers some advantages. The method avoids the
use of high temperature curing, which may not be suitable for heat
sensitive drugs or polymers used in medical device coatings. Also,
the method avoids the use of plasticizers, which allows for lower
temperature curing, but which may not be biocompatible and would
require regulatory approval for use in implantable medical
devices.
[0020] The medical device of the present invention is not limited
to the coronary stents in the disclosed embodiments. Non-limiting
examples of other medical devices that can be used with the coating
methods of the present invention include catheters, guide wires,
balloons, filters (e.g., vena cava filters), stents, stent grafts,
vascular grafts, intraluminal paving systems, pacemakers,
electrodes, leads, defibrillators, joint and bone implants, spinal
implants, vascular access ports, intra-aortic balloon pumps, heart
valves, sutures, artificial hearts, neurological stimulators,
cochlear implants, retinal implants, and other devices that can be
used in connection with therapeutic coatings. Such medical devices
are implanted or otherwise used in body structures, cavities, or
lumens such as the vasculature, gastrointestinal tract, abdomen,
peritoneum, airways, esophagus, trachea, colon, rectum, biliary
tract, urinary tract, prostate, brain, spine, lung, liver, heart,
skeletal muscle, kidney, bladder, intestines, stomach, pancreas,
ovary, uterus, cartilage, eye, bone, and the like.
[0021] The therapeutic agent in the powder coating material, or
coalescing solvent, or the polymer film coating the medical device
may be any pharmaceutically acceptable agent such as a non-genetic
therapeutic agent, a biomolecule, a small molecule, or cells. The
therapeutic agent may be available in powder form, or may be
converted into a powder formulation by any known method including
cryogenic cooling with grinding, drying, micronizing, or spraying
onto the medical device and drying.
[0022] Exemplary non-genetic therapeutic agents include
anti-thrombogenic agents such heparin, heparin derivatives,
prostaglandin (including micellar prostaglandin E1), urokinase, and
PPack (dextrophenylalanine proline arginine chloromethylketone);
anti-proliferative agents such as enoxaparin, angiopeptin,
sirolimus (rapamycin), tacrolimus, everolimus, zotarolimus,
monoclonal antibodies capable of blocking smooth muscle cell
proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory
agents such as dexamethasone, rosiglitazone, prednisolone,
corticosterone, budesonide, estrogen, estrodiol, sulfasalazine,
acetylsalicylic acid, mycophenolic acid, and mesalamine;
anti-neoplastic/anti-proliferative/anti-mitotic agents such as
paclitaxel, epothilone, cladribine, 5-fluorouracil, methotrexate,
doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine,
vincristine, epothilones, endostatin, trapidil, halofuginone, and
angiostatin; anti-cancer agents such as antisense inhibitors of
c-myc oncogene; anti-microbial agents such as triclosan,
cephalosporins, aminoglycosides, nitrofurantoin, silver ions,
compounds, or salts; biofilm synthesis inhibitors such as
non-steroidal anti-inflammatory agents and chelating agents such as
ethylenediaminetetraacetic acid, O,O'-bis (2-aminoethyl)
ethyleneglycol-N,N,N',N'-tetraacetic acid and mixtures thereof;
antibiotics such as gentamycin, rifampin, minocyclin, and
ciprofloxacin; antibodies including chimeric antibodies and
antibody fragments; anesthetic agents such as lidocaine,
bupivacaine, and ropivacaine; nitric oxide; nitric oxide (NO)
donors such as linsidomine, molsidomine, L-arginine,
NO-carbohydrate adducts, polymeric or oligomeric NO adducts;
anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD
peptide-containing compound, heparin, antithrombin compounds,
platelet receptor antagonists, anti-thrombin antibodies,
anti-platelet receptor antibodies, enoxaparin, hirudin, warfarin
sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet
aggregation inhibitors such as cilostazol and tick antiplatelet
factors; vascular cell growth promotors such as growth factors,
transcriptional activators, and translational promotors; vascular
cell growth inhibitors such as growth factor inhibitors, growth
factor receptor antagonists, transcriptional repressors,
translational repressors, replication inhibitors, inhibitory
antibodies, antibodies directed against growth factors,
bifunctional molecules consisting of a growth factor and a
cytotoxin, bifunctional molecules consisting of an antibody and a
cytotoxin; cholesterol-lowering agents; vasodilating agents; agents
which interfere with endogenous vascoactive mechanisms; inhibitors
of heat shock proteins such as geldanamycin; angiotensin converting
enzyme (ACE) inhibitors; beta-blockers; .beta.AR kinase (.beta.ARK)
inhibitors; phospholamban inhibitors; protein-bound particle drugs
such as ABRAXANE.TM.; and any combinations and prodrugs of the
above.
[0023] Exemplary biomolecules include peptides, polypeptides and
proteins; oligonucleotides; nucleic acids such as double or single
stranded DNA (including naked and cDNA), RNA, antisense nucleic
acids such as antisense DNA and RNA, small interfering RNA (siRNA),
and ribozymes; genes; carbohydrates; angiogenic factors including
growth factors; cell cycle inhibitors; and anti-restenosis agents.
Nucleic acids may be incorporated into delivery systems such as,
for example, vectors (including viral vectors), plasmids or
liposomes.
[0024] Non-limiting examples of proteins include serca-2 protein,
monocyte chemoattractant proteins (MCP-1) and bone morphogenic
proteins ("BMP's"), such as, for example, BMP-2, BMP-3, BMP-4,
BMP-5, BMP-6 (VGR-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11,
BMP-12, BMP-13, BMP-14, BMP-15. Preferred BMP's are any of BMP-2,
BMP-3, BMP-4, BMP-5, BMP-6, and BMP-7. These BMPs can be provided
as homodimers, heterodimers, or combinations thereof, alone or
together with other molecules. Alternatively, or in addition,
molecules capable of inducing an upstream or downstream effect of a
BMP can be provided. Such molecules include any of the "hedghog"
proteins, or the DNA's encoding them. Non-limiting examples of
genes include survival genes that protect against cell death, such
as anti-apoptotic Bcl-2 family factors and Akt kinase; serca 2
gene; and combinations thereof. Non-limiting examples of angiogenic
factors include acidic and basic fibroblast growth factors,
vascular endothelial growth factor, epidermal growth factor,
transforming growth factors .alpha. and .beta., platelet-derived
endothelial growth factor, platelet-derived growth factor, tumor
necrosis factor .alpha., hepatocyte growth factor, and insulin-like
growth factor. A non-limiting example of a cell cycle inhibitor is
a cathespin D (CD) inhibitor. Non-limiting examples of
anti-restenosis agents include p15, p16, p18, p19, p21, p27, p53,
p57, Rb, nFkB and E2F decoys, thymidine kinase and combinations
thereof and other agents useful for interfering with cell
proliferation.
[0025] Exemplary small molecules include hormones, nucleotides,
amino acids, sugars, and lipids and compounds have a molecular
weight of less than 100 kD.
[0026] Exemplary cells include stem cells, progenitor cells,
endothelial cells, adult cardiomyocytes, and smooth muscle cells.
Cells can be of human origin (autologous or allogenic) or from an
animal source (xenogenic), or genetically engineered. Non-limiting
examples of cells include side population (SP) cells, lineage
negative (Lin.sup.-) cells including Lin.sup.-CD34.sup.-,
Lin-CD34.sup.+, Lin.sup.-cKit.sup.+, mesenchymal stem cells
including mesenchymal stem cells with 5-aza, cord blood cells,
cardiac or other tissue derived stem cells, whole bone marrow, bone
marrow mononuclear cells, endothelial progenitor cells, skeletal
myoblasts or satellite cells, muscle derived cells, go cells,
endothelial cells, adult cardiomyocytes, fibroblasts, smooth muscle
cells, adult cardiac fibroblasts +5-aza, genetically modified
cells, tissue engineered grafts, MyoD scar fibroblasts, pacing
cells, embryonic stem cell clones, embryonic stem cells, fetal or
neonatal cells, immunologically masked cells, and teratoma derived
cells.
[0027] Any of the therapeutic agents may be combined to the extent
such combination is biologically compatible.
[0028] The polymers used in the present invention may be available
in powder form, or converted into a powder formulation by any
method known in the art. The polymers may be biodegradable or
non-biodegradable. Non-limiting examples of suitable
non-biodegradable polymers include polystrene; polystyrene maleic
anhydride;
poly(methylmethacrylate-butylacetate-methylmethacrylate);
polyisobutylene copolymers; styrene-isobutylene block copolymers
such as styrene-isobutylene-styrene tri-block copolymers (SIBS) and
other block copolymers such as styrene-ethylene/butylene-styrene
(SEBS); polyvinylpyrrolidone including cross-linked
polyvinylpyrrolidone; polyvinyl alcohols, copolymers of vinyl
monomers such as EVA; polyvinyl ethers; polyvinyl aromatics;
polyethylene oxides; polyesters including polyethylene
terephthalate; polyamides; polyacrylamides; polyethers including
polyether sulfone; polyalkylenes including polypropylene,
polyethylene and high molecular weight polyethylene; polyurethanes;
polycarbonates, silicones; siloxane polymers; cellulosic polymers
such as cellulose acetate; polymer dispersions such as polyurethane
dispersions (BAYHYDROL.RTM.); squalene emulsions; and mixtures and
copolymers of any of the foregoing.
[0029] Non-limiting examples of suitable biodegradable polymers
include polycarboxylic acid, polyanhydrides including maleic
anhydride polymers; polyorthoesters; poly-amino acids; polyethylene
oxide; polyphosphazenes; polylacetic acid, polyglycolic acid and
copolymers and mixtures thereof such as poly(L-lacetic acid)
(PLLA), poly(D,L,-lactide), poly(lacetic acid-co-glycolic acid),
50/50 (DL-lactide-co-glycolide); polydioxanone; polypropylene
fumarate; polydepsipeptides; polycaprolactone and co-polymers and
mixtures thereof such as poly(D,L-lactide-co-caprolactone) and
polycaprolactone co-butylacrylate; polyhydroxybutyrate valerate and
blends; polycarbonates such as tyrosine-derived polycarbonates and
arylates, polyiminocarbonates, and polydimethyltrimethylcarbonates;
cyanoacrylate; calcium phosphates; polyglycosaminoglycans;
macromolecules such as polysaccharides (including hyaluronic acid;
cellulose, and hydroxypropylmethyl cellulose; gelatin; starches;
dextrans; alginates and derivatives thereof), proteins and
polypeptides; and mixtures and copolymers of any of the foregoing.
The biodegradable polymer may also be a surface erodable polymer
such as polyhydroxybutyrate and its copolymers, polycaprolactone,
polyanhydrides (both crystalline and amorphous), maleic anhydride
copolymers, and zinc-calcium phosphate.
[0030] A variety of solvents may be used as the coalescing solvent
in the present invention including methanol, ethanol, N-propanol,
isopropanol, butoxydiglycol, butoxyethanol, butoxyisopropanol,
butoxypropanol, n-butyl alcohol, t-butyl alcohol, butylene glycol,
butyl octanol, diethylene glycol, dimethoxydiglycol, dimethyl
ether, dipropylene glycol, ethoxydiglycol, ethoxyethanol, ethyl
hexane diol, glycol, hexane diol, 1,2,6-hexane triol, hexyl
alcohol, hexylene glycol, isobutoxy propanol, isopentyl diol,
3-methoxybutanol, methoxydiglycol, methoxyethanol,
methoxyisopropanol, methoxymethylbutanol, methoxy PEG-10, methylal,
methyl hexyl ether, methyl propane diol, neopentyl glycol, PEG-4,
PEG-6, PEG-7, PEG-8, PEG-9, PEG-6-methyl ether, pentylene glycol,
PPG-7, PPG-2-buteth-3, PPG-2 butyl ether, PPG-3 butyl ether, PPG-2
methyl ether, PPG-3 methyl ether, PPG-2 propyl ether, propane diol,
propylene glycol, propylene glycol butyl ether, propylene glycol
propyl ether, tetrahydrofuran, trimethyl hexanol, phenol, benzene,
toluene, xylene; as well as water, if necessary in mixture with
dispersants and mixtures of the above-named substances.
[0031] While the various elements of the disclosed invention are
described and/or shown in various combinations and configurations,
which are exemplary, other combinations and configurations,
including more, less or only a single embodiment, are also within
the spirit and scope of the present invention.
* * * * *